A programme to develop a skin patch containing two medicines (physostigmine and hyoscine), Study 6: Assessment of blood levels of the two medicines and any associated symptoms in healthy female participants.
- Conditions
- Potential risk of poisoning by nerve agentInjury, Occupational Diseases, Poisoning
- Registration Number
- ISRCTN15358284
- Lead Sponsor
- Dstl
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Male
- Target Recruitment
- 36
Screening (all periods):
1. Ability to give written informed consent prior to study participation
2. Healthy Caucasian female subjects aged between 18 and 45 years (inclusive)
3. A female with a documented record of surgical sterilisation, or of child-bearing potential could be enrolled provided she:
3.1. Had a negative pregnancy test prior to entry into the study and agreed not to attempt to become pregnant during the study.
3.2. Is routinely using adequate hormonal contraception (including hormonal implants, depot injections, and hormone-impregnated IUDs when supplemented by a barrier method) which had not been changed in the three months before the study; agreed to continue to do so during the study, and agreed to use an additional barrier method for the duration of the study and for 28 days after study completion
3.3. Is not breastfeeding
4. Body Mass Index (BMI) within the range of =21 and =30 kg/m²
5. Individual vital signs must be within the following ranges:
5.1. Pulse rate 50-90 bpm
5.2. Systolic blood pressure 100-140 mmHg
5.3. Diastolic blood pressure 50-90 mmHg
6. Ability to communicate well with the investigator and comply with the requirements of the study
7. Subjects intending to take part in two study periods must agree not to take part in another clinical study involving blood sampling for a further 4 months (due to the relatively high amount of blood required for this study)
Screening (all periods):
1. Presence of any clinically significant medical condition as determined by the Investigator
2. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug (e.g. renal or liver disease, respiratory, immunological, endocrine or neurological disorders).
3. Any clinically-significant ECG abnormality other than sinus bradycardia or respiratory sinus arrhythmia
4. Evidence of postural hypotension (BP measurement after 5 minutes supine and again after 2 minutes standing, defined as a decrease between the two measurements of more than 20 mmHg (systolic)
5. Known or suspected hypersensitivity or idiosyncratic reaction related to any of the study products
6. Any history of contact dermatitis
7. A dibucaine number of less than 70
8. Any skin disorder, broken skin, scars, tattoos at the sites of patch application (i.e. on both arms, if volunteer planned to take part in more than one patch administration)
9. Glaucoma or a history of glaucoma in first-degree relatives (i.e. parents, siblings or offspring)
10. Presence of Anterior Chamber Narrow Angle (Van Herrick Grade 1 and 2)
11. Intra-ocular pressure exceeding 20 mmHg
12. Uncorrected vision in either eye of worse than 6/9 on the Snellen Scale
13. Corrected vision of 6/9 or better on the Snellen Scale when wearing +2.25 dioptre reading glasses.
14. Require glasses or contact lenses for distance vision
15. History of asthma (within the previous 10 years), exercise induced bronchospasm or relevant seasonal bronchospasm
16. Lung function of less than 80% of predicted FEV1 and FVC values
17. History or evidence of drug abuse (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates)
18. Positive test for HIV, Hepatitis B surface antigen or Hepatitis C antibody
19. History or evidence of alcohol abuse defined as an intake of more than 21 units per week (where 1 unit corresponds to 250 ml beer, 20 ml spirits/liqueur or one glass (100 ml) of wine)
20. Positive urine test for alcohol
21. Participation in another clinical study within the last three months
22. Use of any prescription medication within the last 14 days (with the exception of hormonal contraception)
23. Use of non-prescription medication that may have impacted the safety aspects and objectives of the study, within the last 7 days (apart from paracetamol)
24. Donation of blood or blood products within the last 3 months, or the intention to donate blood or blood products within 3 months after completion of the study if taking part in one study period or donated blood or blood products within 4 months after completion of the study if taking part in two study periods
Baseline (all periods):
1. Evidence of postural hypotension (BP measurement after 5 minutes supine and again after 2 minutes standing, defined as a decrease between the two measurements of more than 20 mmHg (systolic)
2. Development of any exclusion criteria since last visit
3. Positive urine test for alcohol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The safety and tolerability of physostigmine/hyoscine transdermal patches assessed by monitoring vital signs, ECG, ocular function (near point), patch application site assessment, using digital photography. Tests performed at intervals for up to 96 hours after patch application and at follow up after periods 1 and 2. In period 3 these safety measures are conducted at up to 240 hours after first patch application and at follow up.
- Secondary Outcome Measures
Name Time Method <br> 1. The pharmacokinetic (PK) and pharmacodynamic (PD) profiles of physostigmine and hyoscine measured in periods 1 and 2 at pre-dose and regular intervals up to 96 hours after patch application. In period 3 the blood levels of these medicines was measured at pre-dose and up to 240 hours after first patch application. Assay by liquid chromatography-tandem mass spectrometry (LC-MS-MS) method. Acetylcholinesterase levels measured at baseline, pre-dose, and intervals up to 240 hours after patch application. Method was validated spectrophotometric method<br><br> 2. The cognitive and ocular effects of physostigmine and hyoscine measured by a set of attention tests and light responsiveness/ vision accommodation tests respectively<br><br>